Cefotaxime
J01D - Other beta-lactam antibacterials
ATC J01DD01
Small molecule
approved 1981
Parenteral
Natural product
🧬 Cross-allergy: Cephalosporins
JFDA label: Taxime 500mg IV/IM Powder for injection IV/IM INJ
Mechanism of Action
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested. Cefotaxime has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria. Enterococcus species may be intrinsically resistant to cefotaxime. Most extended-spectrum beta-lactamase (ESBL)-producing and carbapenemase-producing isolates are resistant to cefotaxime.
Indications
Approved
- Bacteremia/Septicemia
- Bone or joint infections
- CNS infections
- Genitourinary infections
- Gynecologic infections
- Intra-abdominal infections
- Lower respiratory tract infections
- Skin and skin structure infections
- Surgical prophylaxis
Off-label
- Acute bacterial rhinosinusitis
- Bacterial enteric infections in HIV-infected patients (empiric treatment) (adolescents and adults)
- Bite wounds (animal)
- Community-acquired pneumonia (children)
- Disseminated gonococcal infection (DGI) (infants)
- Endocarditis, treatment (pediatric)
- Gonococcal scalp abscesses (infants)
- Gonococcal, disseminated infection (arthritis and arthritis-dermatitis syndrome)
- Lyme neuroborreliosis
- Skin and soft tissue necrotizing infections
Antimicrobial Spectrum
Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16 · curated · openfda-label.
Bacteria
| Organism | Activity | MIC |
|---|---|---|
| Bacteroides fragilis | Active | — |
| Chlamydia trachomatis | Active | — |
| Clostridium difficile | Active | — |
| Enterobacter cloacae | Susceptible | 1.0 mg/L |
| Enterobacterales | Susceptible | 1.0 mg/L |
| Enterococcus faecalis | Active | — |
| Escherichia coli | Susceptible | 1.0 mg/L |
| Fusobacterium nucleatum | Active | — |
| Haemophilus influenzae | Susceptible | 0.125 mg/L |
| Haemophilus influenzae | Susceptible | 0.125 mg/L |
| Haemophilus parainfluenzae | Active | — |
| Klebsiella pneumoniae | Susceptible | 1.0 mg/L |
| Moraxella catarrhalis | Susceptible | 1.0 mg/L |
| Morganella morganii | Active | — |
| Neisseria gonorrhoeae | Susceptible | 0.125 mg/L |
| Neisseria meningitidis | Susceptible | 0.125 mg/L |
| Neisseria meningitidis | Susceptible | 0.125 mg/L |
| Pasteurella multocida | Susceptible | 0.03 mg/L |
| Proteus mirabilis | Active | — |
| Proteus vulgaris | Active | — |
| Providencia rettgeri | Active | — |
| Providencia stuartii | Active | — |
| Salmonella spp. | Susceptible | 1.0 mg/L |
| Salmonella typhi | Active | — |
| Serratia marcescens | Active | — |
| Staphylococcus aureus | Active | — |
| Staphylococcus epidermidis | Active | — |
| Streptococcus pneumoniae | Susceptible | 0.5 mg/L |
| Streptococcus pneumoniae | Susceptible | 0.5 mg/L |
| Streptococcus pyogenes | Active | — |
| Vibrio spp. | Susceptible | 0.25 mg/L |
| Viridans group streptococci | Susceptible | 0.5 mg/L |
| Enterobacter cloacae | Resistant | 2.0 mg/L |
| Escherichia coli | Resistant | 2.0 mg/L |
| Klebsiella pneumoniae | Resistant | 2.0 mg/L |
| Streptococcus pneumoniae | Resistant | 2.0 mg/L |
Class profile
| gramStatus | Both |
|---|---|
| spectrumBreadth | Broad |
| atypicalCoverage | No |
| isBactericidal | 1 |
| moaCategory | Cell wall synthesis inhibitor (beta-lactam, 3rd generation cephalosporin) |
| pdIndex | Time-dependent |
| postAntibioticEffect | None |
| mrsaCoverage | 0 |
| resistanceMechanisms | ESBL production,AmpC beta-lactamase |
Contraindications
Source: Lexicomp
- Hypersensitivity to cefotaxime, any component of the formulation, or other cephalosporins Absolute
Adverse Reactions
Very Common >10%Common 1–10%Uncommon 0.1–1%
Rare 0.01–0.1%Very Rare <0.01%Not Known
Blood and lymphatic system disorders (1)
Common Eosinophilia
Gastrointestinal disorders (4)
Common Colitis · diarrhea · nausea · vomiting
Skin and subcutaneous tissue disorders (2)
Common Pruritus · skin rash
General disorders and administration site conditions (5)
Common Fever · Induration at injection site · inflammation at injection site · pain at injection site · tenderness at injection site
Dosing
Source: Lexicomp
Usual dosage range: IM, IV: Uncomplicated infections: IM, IV: 1 g every 12 hours Moderate-to-severe infections: IM, IV: 1 to 2 g every 8 hours Life-threatening infections: IV: 2 g every 4 hours Acute bacterial rhinosinusitis, severe infection requiring hospitalization: IV: 2 g every 4 to 6 hours for 5 to 7 days (Chow 2012) Arthritis (septic): IV: 1 g every 8 hours Bacterial enteric infections in HIV-infected patients (empiric treatment) (off-label use): IV: 1 g every 8 hours (HHS [OI adult 2015]) Bite wounds (animal) (off-label use): IV: 1 to 2 g every 6 to 8 hours in combination with clindamycin or metronidazole for anaerobic coverage (IDSA [Stevens 2014]) Brain abscess, meningitis: IV: 2 g every 4 to 6 hours in combination with other antimicrobial therapy as warranted (Kowlessar 2006; Tunkel 2004) Cesarean section: IM, IV: 1 g IV as soon as the umbilical cord is clamped, then 1 g IV or IM at 6 and 12 hours after the first dose Complicated community-acquired intra-abdominal infection of mild-to-moderate severity, including hepatic abscess (in combination with metronidazole): IV: 1 to 2 g every 6 to 8 hours for 4 to 7 days (provided source controlled). Note: For severe infections consider other antimicrobial agents (Bradley, 1987; Kim 2010; Solomkin 2010). Gonorrhea, uncomplicated infection of the cervix, urethra, or rectum: Note: CDC STD guidelines do not recommend cefotaxime as a treatment option for uncomplicated gonorrhea; ceftriaxone is the preferred cephalosporin (CDC [Workowski 2015]) Uncomplicated gonorrhea of the cervix or urethra (males or females) or of the rectum (females): Manufacturer’s labeling: IM: 0.5 g as a single dose Uncomplicated gonorrhea of the rectum (males): Manufacturer’s labeling IM: 1 g as a single dose Gonorrhea, disseminated infections (arthritis and arthritis-dermatitis syndrome) (alternative to preferred therapy) (off-label use): IV: 1 g every 8 hours in combination with azithromycin. Continue for 24 to 48 hours after improvement begins, then switch to oral therapy guided by antimicrobial susceptibility testing. Total duration of therapy at least 7 days (CDC [Workowski 2015]) Lyme disease (as an alternative to ceftriaxone): Cardiac manifestations: IV: 2 g every 8 hours for 14 to 21 days (Wormser 2006) CNS manifestations: IV: 2 g every 8 hours for 10 to 28 days (Halperin 2007; Wormser 2006) Pneumonia, community-acquired (CAP): IV: 1 to 2 g every 8 hours (Lim 2009). For critically-ill patients (empiric therapy), use in combination with azithromycin or a respiratory fluoroquinolone (eg, levofloxacin or moxifloxacin) or in non-critically ill patients (empiric therapy), use in combination with a macrolide (preferred) or doxycycline; duration of therapy is ≥5 days (IDSA/ATS [Mandell 2007]) Surgical (perioperative) prophylaxis (off-label use): IV: 1 g within 60 minutes prior to surgical incision. Doses may be repeated in 3 hours if procedure is lengthy or if there is excessive blood loss. Note: preferred agent (with ampic
(For additional information see "Cefotaxime: Pediatric drug information") Usual dosage range for susceptible infections: Infants, Children, and Adolescents: Manufacturer's labeling: ≥50 kg: Refer to adult dosing Alternate recommendations (Red Book [AAP] 2012): IM, IV: Mild to moderate infection: 50 to 180 mg/kg/day in divided doses every 6 to 8 hours (maximum dose: 6 g daily) Severe infection: 200 to 225 mg/kg/day in divided doses every 4 to 6 hours; up to 300 mg/kg per day has been used for meningitis (maximum dose: 12 g daily) Indication-specific dosing: Acute bacterial rhinosinusitis, severe infection requiring hospitalization (off-label use): Children: IV: 100 to 200 mg/kg/day divided every 6 hours for 10 to 14 days (Chow 2012) Arthritis (septic): Children ≥50 kg or Adolescents: Refer to adult dosing. Bacterial enteric infections in HIV-infected patients (empiric treatment) (off-label use): Adolescents: IV: Refer to adult dosing. Brain abscess: Children ≥50 kg or Adolescents: Refer to adult dosing. Cesarean section: Children ≥50 kg or Adolescents: Refer to adult dosing. Complicated community-acquired intra-abdominal infection (in combination with metronidazole): Infants and Children: IV: 150 to 200 mg/kg/day divided every 6 to 8 hours (Solomkin 2010) Endocarditis, treatment (off-label use): Children and Adolescents: IV: 200 mg/kg/day in divided doses every 6 hours; maximum daily dose: 12 g/day; treat for at least 4 to 6 weeks; longer durations may be necessary; may use in combination with gentamicin for some organisms (AHA [Baltimore 2015]) Gonorrhea (off-label use): Disseminated gonococcal infection (DGI): IV, IM: 25 mg/kg every 12 hours for 7 days; continue for 10 to 14 days if meningitis is documented (CDC [Workowski 2015]) Gonococcal scalp abscesses: IV, IM: 25 mg/kg every 12 hours for 7 days (CDC [Workowski 2015]) Disseminated infections (arthritis and arthritis-dermatitis syndrome) (alternative to preferred therapy): Adolescents: Refer to adult dosing. Lyme disease (as an alternative to ceftriaxone): Cardiac or CNS manifestations: Infants and Children: IV: 150 to 200 mg/kg/day in divided doses every 6 to 8 hours for 14 to 28 days; maximum daily dose: 6 g daily (Halperin 2007; Wormser 2006) Meningitis (in combination with vancomycin): Infants and Children: IV: 225 to 300 mg/kg/day in divided doses every 6 to 8 hours (Tunkel 2004) Pneumonia, community-acquired (IDSA/PIDS 2011): Infants >3 months and Children: IV: Note: May consider addition of vancomycin or clindamycin to empiric therapy if community-acquired MRSA suspected. In children ≥5 years, a macrolide antibiotic should be added if atypical pneumonia cannot be ruled out. Empiric treatment, Haemophilus influenzae, group A Streptococcus, or S. pneumoniae (MICs to penicillin ≤2.0 mcg/mL), patient fully immunized for H. influenzae type b and S. pneumoniae, or minimal local resistance to penicillin in invasive pneumococcal strains (alternative to ampicillin or penicillin): 50 mg/kg/dose
Refer to adult dosing.
Manufacturer’s labeling: Note: Renal function may be estimated using Cockcroft-Gault formula for dosage adjustment purposes. CrCl 2: Dose should be decreased by 50%. Dialysis: Moderately dialyzable (20% to 50%) Alternate recommendations: Adults: The following dosage adjustments have been used by some clinicians (Aronoff 2007; Heintz 2009; Trotman 2005): GFR >50 mL/minute: Administer every 6 hours (Aronoff 2007) GFR 10 to 50 mL/minute: Administer every 6 to 12 hours (Aronoff 2007) GFR or decrease the dose by 50% (and administer at usual intervals) (Aronoff 2007) Intermittent hemodialysis (IHD): Administer 1 to 2 g every 24 hours (on dialysis days, administer after hemodialysis). Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions (Heintz 2009). Peritoneal dialysis (PD): 1 g every 24 hours (Aronoff 2007) Continuous renal replacement therapy (CRRT) (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment: CVVH: 1 to 2 g every 8 to 12 hours CVVHD: 1 to 2 g every 8 hours CVVHDF: 1 to 2 g every 6 to 8 hours Children: Note: Glomerular filtration rate (GFR) should be estimated using an acceptable pediatric method (eg, Schwartz equation, Traub-Johnson equation, or a height/weight nomogram): The following dosage adjustments have been used by some clinicians (Aronoff 2007): GFR 30 to 50 mL/minute/1.73 m2: 35 to 70 mg/kg/dose every 8 to 12 hours GFR 10 to 29 mL/minute/1.73 m2: 35 to 70 mg/kg/dose every 12 hours GFR 2: 35 to 70 mg/kg/dose every 24 hours Intermittent hemodialysis (IHD): 35 to 70 mg/kg/dose every 24 hours Peritoneal dialysis: 35 to 70 mg/kg/dose every 24 hours Continuous renal replacement therapy (CRRT): 35 to 70 mg/kg/dose every 12 hours
There are no dosage adjustments provided in the manufacturer’s labeling.
Warnings & Precautions
Source: Lexicomp
Arrhythmia
A potentially life-threatening arrhythmia has been reported in patients who received a rapid (• Granulocytopenia: Granulocytopenia and more rarely agranulocytosis may develop during prolonged treatment (>10 days).
Penicillin allergy
Use with caution in patients with a history of penicillin allergy, especially IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria).
Superinfection
Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Tissue inflammation
Minimize tissue inflammation by changing infusion sites when needed. Disease-related concerns:
Colitis
Use with caution in patients with a history of colitis.
Renal impairment
Use with caution in patients with renal impairment; dosage adjustment may be required. Concurrent drug therapy issues:
Drug-drug interactions
Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Pregnancy & Lactation
Pregnancy
FDA category B
Adverse events have not been observed in animal reproduction studies. Cefotaxime crosses the human placenta and can be found in fetal tissue. An increase in most types of birth defects was not found following first trimester exposure to cephalosporins. During pregnancy, peak cefotaxime serum concentrations are decreased and the serum half-life is shorter. Cefotaxime is approved for use in women undergoing cesarean section (consult current guidelines for appropriate use).
Lactation
Low concentrations of cefotaxime are found in breast milk. The manufacturer recommends that caution be exercised when administering cefotaxime to nursing women. Nondose-related effects could include modification of bowel flora. The pregnancy-related changes in cefotaxime pharmacokinetics continue into the early postpartum period.
Monitoring
| Efficacy | Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin) |
|---|---|
| Toxicity | Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea) |
| Clinical pearl | Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship). |
| Counseling | Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h. |
Chemistry & Properties
| Formula | C16H17N5O7S2 |
|---|---|
| Molecular weight | 455.47 g/mol |
| IUPAC name | (6R,7R)-3-(acetyloxymethyl)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid |
| CAS | 63527-52-6 |
| PubChem CID | 5742673 |
| InChIKey | GPRBEKHLDVQUJE-QSWIMTSFSA-N |
| logP | -0.62 (XLogP -1.4) |
| Polar surface area | 173.51 Ų |
| H-bond acceptors / donors | 11 / 3 |
| Drug-likeness (QED) | 0.21 |
| Lipinski violations | 1 |
SMILES
CO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)O)=C(COC(C)=O)CS[C@H]12)c1csc(N)n1Biology & Pharmacokinetics
Pharmacokinetics
| BBB penetrant | No |
|---|
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP2C8 | Inhibitor | — |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OAT1 (Inhibitor)OAT2 (Inhibitor)OAT3 (Inhibitor)OAT4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)PEPT1 (Inhibitor)PEPT2 (Inhibitor)OAT (Substrate)OAT1 (Substrate)OAT2 (Substrate)OAT3 (Substrate)OAT4 (Substrate)P-gp (Substrate)PEPT1 (Substrate)
Drug–drug interactions (14, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Amikacin | moderate | |
| Amikacin (liposome) | moderate | |
| Chloramphenicol | moderate | |
| Dicoumarol | moderate | |
| Ethinylestradiol | moderate | |
| Gentamicin | moderate | |
| Kanamycin | moderate | |
| Mycophenolic acid | moderate | |
| Neomycin | moderate | |
| Pemetrexed | moderate | |
| Picosulfuric acid | moderate | |
| Porfimer sodium | moderate | |
| Streptomycin | moderate | |
| Warfarin | moderate |
Registered Products (12)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Cefotax 0.5 gm Vial | Vial as Sodium 0.5 g | 1 vial | AL-Faiasel Drug Store | 1.590 |
| Cefotax 1gm Vial | Vial as Sodium 1 g | 1 vial | AL-Faiasel Drug Store | 2.490 |
| Primocef | Ampoule 500 mg | 1 vial | Professional Drug Store | 2.950 |
| Taxime | Ampoule 500 mg, 1 % | 1 amp pack varies | Pharma International Company/ Jordan | 3.100 |
| Taxime 500mg IV/IM Powder for injection IV/IM INJ | Powder for Injection 500 mg, 1 % | 5 ml pack varies | Pharma International Company/ Jordan | 3.100 |
| Primocef 1gm I.M Injection | Powder for Injection 1 g | 1 vial pack varies | Professional Drug Store | 5.370 |
| Primocef 1gm I.V Inj | Powder for Injection 1 g | 1 amp pack varies | Professional Drug Store | 5.370 |
| Taxime 1gm | Ampoule 1 g, 1 % | 5 ml pack varies | Pharma International Company/ Jordan | 5.830 |
| Taxime 1gm Powder For IV Injection | Powder for Injection 1 g | 1 vial pack varies | Pharma International Company/ Jordan | 5.830 |
| Taxime1g IV/IM Powder for injection IV/IM INJ | Powder for Injection 1 g, 1 % | 5 ml pack varies | Pharma International Company/ Jordan | 5.830 |
| Taxime 500mg IV/IM Powder for injection IV/IM INJ | Powder for Injection 500 mg | 10 vial | Pharma International Company/ Jordan | 27.900 |
| Taxime1g IV/IM Powder for injection IV/IM INJ | Powder for Injection 1 g | 10 vial pack varies | Pharma International Company/ Jordan | 52.470 |